title: The proteolytic YB-1 fragment interacts with DNA repair machinery and enhances survival during DNA damaging stress.
abstract: The Y-box binding protein 1 (YB-1) is a DNA/RNA-binding nucleocytoplasmic shuttling protein whose regulatory effect on many DNA and RNA-dependent events is determined by its localization in the cell. We have shown previously that YB-1 is cleaved by 20S proteasome between E219 and G220, and the truncated N-terminal YB-1 fragment accumulates in the nuclei of cells treated with DNA damaging drugs. We proposed that appearance of truncated YB-1 in the nucleus may predict multiple drug resistance. Here, we compared functional activities of the full-length and truncated YB-1 proteins and showed that the truncated form was more efficient in protecting cells against doxorubicin treatment. Both forms of YB-1 induced changes in expression of various genes without affecting those responsible for drug resistance. Interestingly, although YB-1 cleavage did not significantly affect its DNA binding properties, truncated YB-1 was detected in complexes with Mre11 and Rad50 under genotoxic stress conditions. We conclude that both full-length and truncated YB-1 are capable of protecting cells against DNA damaging agents, and the truncated form may have an additional function in DNA repair.
authors.affiliation: Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation.
authors.forename: Ekaterina R
authors.initials: ER
authors.lastname: Kim
authors.affiliation: Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation; University of Tartu; Institute of Technology; Tartu, Estonia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Selyutina
authors.affiliation: Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Buldakov
authors.affiliation: Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation; Department of Molecular Oncology; British Columbia Cancer Research Centre; Vancouver, British Columbia, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Evdokimova
authors.affiliation: Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation.
authors.forename: Lev P
authors.initials: LP
authors.lastname: Ovchinnikov
authors.affiliation: Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Sorokin
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D051379:Mice; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D004317:Doxorubicin; D004247:DNA; D046988:Proteasome Endopeptidase Complex
keywords: DNA damage; DNA reparation; PEST; YB-1; cleavage; drug resistance; nuclear localization; proteasome; truncation